15-55430734-T-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130810.4(DNAAF4):​c.1199A>T​(p.Lys400Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K400N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNAAF4
NM_130810.4 missense

Scores

2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Publications

0 publications found
Variant links:
Genes affected
DNAAF4 (HGNC:21493): (dynein axonemal assembly factor 4) This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in the developing neocortex. A chromosomal translocation involving this gene is associated with a susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream cell cycle progression 1 (CCPG1) gene. [provided by RefSeq, Mar 2011]
DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16935915).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAAF4NM_130810.4 linkc.1199A>T p.Lys400Ile missense_variant Exon 10 of 10 ENST00000321149.7 NP_570722.2 Q8WXU2-1
DNAAF4NM_001033559.3 linkc.1093A>T p.Lys365* stop_gained Exon 9 of 9 NP_001028731.1 Q8WXU2-3
DNAAF4NM_001033560.2 linkc.1047+4171A>T intron_variant Intron 8 of 8 NP_001028732.1 Q8WXU2-2A0A0S2Z5Z4
DNAAF4-CCPG1NR_037923.1 linkn.1408+1763A>T intron_variant Intron 8 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAAF4ENST00000321149.7 linkc.1199A>T p.Lys400Ile missense_variant Exon 10 of 10 1 NM_130810.4 ENSP00000323275.3 Q8WXU2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461192
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726934
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33454
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26104
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39570
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86238
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53364
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111630
Other (OTH)
AF:
0.00
AC:
0
AN:
60348
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T;T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.70
T;.
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.0
T
PhyloP100
1.0
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.4
.;N
REVEL
Benign
0.068
Sift
Benign
0.21
.;T
Sift4G
Benign
0.14
T;T
Polyphen
0.059
B;B
Vest4
0.31
MutPred
0.48
Loss of ubiquitination at K400 (P = 0.0167);Loss of ubiquitination at K400 (P = 0.0167);
MVP
0.86
MPC
0.12
ClinPred
0.35
T
GERP RS
0.27
Varity_R
0.099
gMVP
0.29
Mutation Taster
=132/68
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs763437062; hg19: chr15-55722932; API